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Biomedical subjects

S P Lim

Publications and source records attributed to S P Lim.

At least 37 records · Page 2Linked to original sources
PubMed1991

Action of acetylcholine on smooth muscle.

Contraction of smooth muscle by acetylcholine is mediated by activation of muscarinic receptors of which M2 and M3 subtypes are present in longitudinal muscle of guinea pig intestine. In single cells, muscarinic receptor activation evokes calcium release from stores which raises the internal free calcium concentration and causes opening of calcium-activated potassium channels. The rise in internal calcium suppresses the voltage-dependent inward calcium current. A third important effect is the opening of channels which cause depolarization of the membrane and so increase action potential discharge and contraction in the whole muscle. These channels were studied by voltage-clamp of single cells from longitudinal muscle of rabbit small intestine. They were found to be permeable to Na and K but not detectably permeable to Cl. They can pass Ca but the amount entering the cell is not sufficient to raise the internal calcium concentration appreciably.

Acetylcholine↗
PubMed1990

Improvement in exercise performance and hemodynamics by labetalol in patients with idiopathic dilated cardiomyopathy.

Labetalol, a combined alpha- and beta-blocking agent, was administered to 12 patients (mean age 55 years) with idiopathic dilated cardiomyopathy to examine its effects on symptomatology and exercise performance. Studies were performed before treatment, after 8 weeks of placebo, and after 8 weeks of labetalol therapy in a randomized, crossover, double-blind design. The mean (+/- SEM) dose of labetalol for the group was 275 +/- 29 mg. Compared to treatment with placebo, the maximum duration of symptom-limited exercise was significantly prolonged with labetalol (580 +/- 72 seconds to 683 +/- 71 seconds; p less than 0.005). Both the resting and peak exercise heart rate and systolic blood pressure were significantly reduced. Ascending aortic blood flow velocity was also measured by continuous-wave Doppler technique during exercise. Compared to placebo, treatment with labetalol conferred no significant change in cardiac output at rest but significantly improved cardiac output at maximum exercise (14 +/- 3%; p less than 0.001). Doppler-derived peak aortic flow velocity, acceleration, and flow velocity integral were also significantly improved at maximum exercise. Systemic vascular resistance, as derived from mean blood pressure/cardiac output, was reduced by 12 +/- 3% and 16 +/- 3% at rest and at maximum exercise, respectively. New York Heart Association functional class was improved (3.2 +/- 0.2 to 2.2 +/- 0.3; p less than 0.005). No major side effects from labetalol were encountered. Thus labetalol improves symptomatology, exercise capacity, and exercise hemodynamics and reduces systemic vascular resistance in patients with idiopathic dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed1989

Properties of calcium stores and transient outward currents in single smooth muscle cells of rabbit intestine.

1. Single dispersed cells obtained by collagenase treatment of longitudinal muscle of rabbit small intestine were voltage clamped with low-resistance patch pipettes and membrane current was measured. 2. In cells held at -20 or -30 mV, a discharge of spontaneous transient outward currents (STOCs) was usually seen; these are believed to represent the sporadic release of calcium from storage sites in the cell in relation to TEA-sensitive, 4 AP-resistant, calcium-activated potassium channels. 3. Caffeine (20 mM) externally applied, accelerated and then abolished STOCs; carbachol (0.1 mM) had similar effects; the initial burst of STOCs was often carried on a large, temporary, outward current which could occur alone. This was suggested to be caused by the rapid release of stored calcium in relation to calcium-activated potassium channels. 4. If STOCs were abolished by caffeine (or carbachol) then carbachol (or caffeine) did not evoke outward current indicating that these drugs act on the same calcium store but by different pathways. Inclusion of ryanodine (10(-8)-10(-4) M) in the patch pipette abolished STOCs soon after establishing whole-cell recording mode; afterwards, outward current to caffeine or to carbachol could not be evoked. 5. STOCs were quickly abolished in cells patched with pipettes filled with GTP gamma S (0.1-1 mM) or Gpp(NH)p (0.1-1 mM) but were large or normal in size in cells where GDP beta S (0.1-1 mM) was included in the pipette. GTP gamma S or Gpp(NH)p in the cell abolished outward current to caffeine or to carbachol, but had no effect on calcium-activated potassium channel activity in isolated patches or on a TEA-sensitive, 4-AP-resistant, outward potassium current evoked in single cells by stepping positively from a -20 mV holding potential. These results suggest that the effect of guanine nucleotide analogues are on the calcium store rather than on calcium-activated potassium channels. 6. The effects of GTP gamma S or Gpp(NH)p could be explained if they depleted calcium stores via a G-protein mechanism; this effect may involve activation of phospholipase C enzyme (PLC) and D-myo-inositol 1,4,5-trisphosphate (IP3) production as well as a direct effect on stores. However a separate G-protein-independent pathway of activation of PLC by muscarinic receptor activation may exist as calcium release by carbachol was large or normal in cells filled with GDP beta S.

Action Potentials↗
PubMed1989

Mechanism of calcium channel block by D600 in single smooth muscle cells from rabbit ear artery.

This study investigated the action of the calcium antagonist D600 on calcium channel currents recorded in high barium solution from single, enzymatically isolated smooth muscle cells from the rabbit ear artery using the whole cell configuration of the patch-clamp technique. D600 (1-100 microM) was applied by path perfusion or by a new technique that allowed a concentration jump during the current. Application of D600 at rest (holding potential, -60 mV) did not alter the peak inward current elicited on depolarization, but the activation of the channels led to a marked block and an acceleration of the current decay. The mechanism of block of calcium channels by D600 was studied by using pulse protocols with different pulse length and different interpulse intervals. The results were consistent with the hypothesis that D600 has a low affinity for the calcium channels in the resting state and that they have to pass to the open state before the drug affects the calcium channel current. A fast onset of the calcium channel block by D600 (time constant, 502 msec) could be shown by rapid application of D600 during the sustained current component of the barium inward current. However, experiments did not definitely distinguish whether binding occurred to the open or to the inactivated state (although there was some evidence of a long-lasting binding to an inactivated state).

Animals↗
PubMed1988

Action of nifedipine or BAY K8644 is dependent on calcium channel state in single smooth muscle cells from rabbit ear artery.

The actions of nifedipine or BAY K 8644 were studied on barium currents recorded from single, collagenase- and elastase-dispersed, smooth muscle cells from the rabbit ear artery using the whole-cell configuration of the patch-clamp technique. Nifedipine (3 microM) caused a reduction in the barium current (IBa) evoked by steps to potentials positive of -10 mV. This was characterized by a pronounced 'initial' block, an increase in the rate of current decay during the voltage-clamp step, but by no increase in block if pulses were repeated every 600 ms. Rapid extracellular application of nifedipine (1 microM) during the sustained current component (using a new concentration-jump technique) was found to have no effect on IBa over 4s at +20 mV, but after returning to the holding potential (-60 mV) for 10s, sustained IBa was subsequently abolished. BAY K 8644 (1 microM) increased IBa at all potentials, and on rapid application during the sustained current component markedly potentiated IBa. The results suggest that nifedipine binds with high affinity to the closed, available state of the Ca++ channels but they do not suggest binding to the open or inactivated states. The effect of BAY K 8644 is consistent with high affinity binding to the open or inactivated and to the closed, available states.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

A calcium-dependent rather than a G-protein mechanism is involved in the inward current evoked by muscarinic receptor stimulation in dialysed single smooth muscle cells of small intestine.

A role of internal calcium was found in the inward current response of single, dispersed, smooth muscle cells to muscarinic receptor activation but no obligatory role for guanine nucleotide binding proteins, in contrast to their obligatory role in muscarinic responses in heart and other tissues.

Animals↗
PubMed1988

Calcium channels and calcium-mediated effects in smooth muscle cells.

In single smooth muscle cells held at depolarized potentials under voltage-clamp, spontaneous transient outward currents (STOCs) of about 100 ms in duration and 100-300 pA in size are observed. These behave as if they are caused by the cyclical release of calcium from storage sites within the cell and can therefore be used as a method of monitoring the release of calcium from these stores by various agents. Muscarinic receptor activation or caffeine applied to single smooth muscle cells from rabbit jejunum produced outward current, probably due to the release of calcium from stores, and STOCs were subsequently abolished. Levels of inositol 1,4,5 trisphosphate in fragments of the muscle were increased within 5 s by carbachol application. STOCs and outward current due to calcium store release were probably due to the opening of calcium-activated K-channels since they were abolished by 4 mM tetraethylammonium. Receptor activation also opens channels that admit cations, including calcium, which may also contribute to tension generation.

Animals↗
PubMed1987

Effects of hypohydration on lung functions in humans.

We studied lung function tests during euhydration (Days 1 and 2), hypohydration (Days 3 and 4), and rehydration (Days 5, 6, and 7) in 6 normal subjects. Hypohydration was induced by administering chlorthalidone, and this resulted in a 4.5% loss of body weight. During hypohydration, lung volumes increased significantly. Interestingly, ventilatory lung function tests including peak expiratory flow rate, FEV1, maximal voluntary ventilation, and flow rates at low lung volumes also increased significantly and returned to normal upon rehydration. Diffusing capacity for carbon monoxide remained unchanged. The improvement in ventilatory lung function tests during hypohydration was surprising, and it is suggested that this was related to loss of water within and/or around the airways. This mechanism is opposite to that which occurs in pulmonary edema with excess lung water where reduction in flow rates occurs.

Adult↗
PubMed1987

Nonbacterial thrombotic endocarditis. Two-dimensional echocardiographic features in an autopsy-proven case.

Diffuse thickening with localized nodularity of the aortic valve cusps was noted on two-dimensional echocardiography in a patient dying of massive esophageal variceal bleeding. Autopsy revealed nonbacterial thrombotic endocarditis involving the aortic and tricuspid valves. Two-dimensional echocardiography can assist in establishing the antemortem diagnosis of this condition, thus clarifying the etiology of the associated new murmurs and embolic phenomena.

Aged↗
PubMed1986

Neuroeffector transmission in the guinea-pig internal anal sphincter: an electrical and mechanical study.

ATP (10(-7)-10(-4) M), ADP (10(-7)-10(-4) M), AMP (10(-7)-10(-4) M) and adenosine (10(-6)-10(-4) M) each hyperpolarized the membrane, inhibited spontaneous spike discharge and relaxed the guinea-pig internal anal sphincter. All experiments were carried out using intracellular microelectrode and simultaneous tension recording techniques in the presence of phentolamine (10(-6) M) and atropine (10(-6) M). ATP was the most effective and produced a concentration-dependent membrane potential change comparable in amplitude to that produced by field stimulation of non-adrenergic non-cholinergic (NANC) nerves. Inhibitory junction potentials, the accompanying relaxations and the responses to ATP (5 X 10(-6)-5 X 10(-5) M) were additive and were increased in K+-deficient and decreased in K+-rich solutions and inhibited by apamin (10(-7) M). A proteolytic enzyme, alpha-chymotrypsin (0.5 U/ml) preferentially antagonized the ability of vasoactive intestinal polypeptide (10(-7) M) to hyperpolarize the membrane and relax the sphincter. The electrical and mechanical responses to ATP (10(-5) M) and inhibitory nerve stimulation were only slightly reduced. The results are consistent with the view that ATP or a related adenine nucleotide may have a transmitter role in the guinea-pig internal anal sphincter.

Adenine Nucleotides↗
PubMed1985

Mechanisms underlying the electrical and mechanical responses of the guinea-pig internal anal sphincter to field stimulation and to drugs.

The electrical membrane characteristics and the response of the circular muscle of the guinea-pig internal anal sphincter (i.a.s.) to field stimulation were studied in vitro using intracellular microelectrodes and conventional mechanical recording techniques. The i.a.s. developed its own tone (3-4 g), following initial stretch (1 g) and spontaneous spike potentials were evident. In the absence of spike potentials, tone declined and disappeared. Tone was not significantly reduced by phentolamine (1 X 10(-6)M). The resting membrane potential, measured between spontaneous spike potentials, was -45 +/- 3.0 mV (n = 224); the space constant (lambda) was 1.13 +/- 0.1 mm (n = 13). Spikes usually overshot by approximately 15 mV. The frequency of spike potential discharge (1-3 Hz) varied with the degree of membrane depolarization, being increased in K+-rich and decreased in K+-deficient solutions or by the presence of Mn2+. It was not significantly affected by C1-withdrawal but was increased in Na+-deficient solutions with or without tetrodotoxin (TTX; 1 X 10(-6)M). Field stimulation (1-20 Hz, 0.5 ms, supramaximal voltage) produced inhibitory junction potentials (i.j.ps) and relaxed tone; at high frequencies (50 Hz or greater), contractions were observed but excitatory junction potentials (e.j.ps) were not. I.j.ps and relaxations were inhibited by apamin (1 X 10(-6)M), TTX (1 X 10(-6)M) but not by atropine (1 X 10(-6)M), phentolamine (1 X 10(-6)M) or hexamethonium (1 X 10(-6)M). I.j.ps were reduced by hyperpolarization and enhanced by depolarization of the membrane by current pulses (15s). The mean equilibrium potential for the i.j.p. was -94 mV (correlation coefficient, gamma = 0.71, n = 5, p less than 0.001). I.j.ps were enhanced in K+-deficient solutions and reduced in K+-rich solutions. Together these results suggest that the i.j.p. is mediated by an increased GK. The absence of [Ca2+]o or the presence of Mn2+ (2 mM) abolished the i.j.p.; in contrast Na+-deficient or C1-free solutions were ineffective in this respect. Tetraethylammonium (5-50mM) abolished the i.j.p.; the accompanying relaxation was reduced by about 80%. The major aspect of the relaxation to nerve stimulation is mediated by membrane hyperpolarization.

Anal Canal↗
PubMed1985

Cardiac prognosis in noncardiac geriatric surgery.

Predictors of perioperative complications, including cardiac death, ventricular tachycardia or fibrillation, and heart failure or myocardial infarction, were assessed in an initial study of 100 patients aged 65 years or older scheduled for elective abdominal or noncardiac thoracic surgery. Preoperative history, results of physical examination, chest roentgenogram, electrocardiogram, laboratory data, Dripps (American Society of Anesthesiologists) class, and Goldman cardiac risk index were compared with rest and exercise radionuclide ventriculograms. Thirteen patients had perioperative cardiac complications, and 6 died. Multivariate analysis showed that an inability to do 2 minutes of bicycle exercise in the supine position to raise the heart rate above 99 beats/min (sensitivity 85%, specificity 64%) gave predictive information not available from clinical or radionuclide data. On prospective testing involving 55 additional geriatric patients, inability to exercise was the only independent predictor of perioperative complications (p less than 0.05). Data from rest and exercise radionuclide ventriculography added little information for predicting perioperative cardiac risk.

Abdomen↗
PubMed1983

Microelectrode recording of the effects of agonists and antagonists on alpha-adrenoceptors on rat somatic nerve terminals.

The effects of apomorphine, catechol, clonidine, isoprenaline, (-)-and (+/-)-noradrenaline, phenylephrine, pyrogallol and xylazine were investigated on the frequency and amplitude of miniature endplate potentials (m.e.p.ps) and, with the exception of apomorphine, catechol and pyrogallol, on the amplitude of endplate potentials (e.p.ps) in the rat phrenic nerve diaphragm preparation. Clonidine, (-)-noradrenaline, phenylephrine and xylazine (each at 1.5 X 10(-5)M) increased m.e.p.p. frequency but not amplitude. The other drugs were ineffective, except isoprenaline (1.5 X 10(-5)M) which enhanced m.e.p.p. amplitude but not frequency. The increase in m.e.p.p. frequency was inhibited by phentolamine, prazosin and yohimbine (each 1.5 X 10(-9)M). Prazosin and yohimbine alone each reduced m.e.p.p. frequency but failed to abolish m.e.p.ps even at high concentrations (10(-3)M). Clonidine, (-)-noradrenaline, phenylephrine and xylazine (each 3 X 10(-6)M) enhanced e.p.p. amplitude; this enhancement was blocked by prazosin and by yohimbine (each 3 X 10(-6)M). In preparations fatigued by prolonged continuous nerve stimulation (5 Hz, 0.05 ms for 30 min), (-)-noradrenaline (3.3 X 10(-4)M) restored m.e.p.p. frequency. The results indicate that adrenoceptors on somatic nerve terminals interact with both alpha 1- and alpha 2-agonists and antagonists and show different characteristics from those at autonomic neuroeffector junctions. The alpha-adrenoceptors on somatic nerve terminals may have an ancilliary physiological role in influencing but not controlling transmitter release.

Adrenergic alpha-Antagonists↗
PubMed1981

Myocardial and peripheral catecholamine responses to acute coronary artery constriction before and after propranolol treatment in the anaesthetised dog.

The left anterior descending coronary artery was constricted for eight minutes on two occasions in 13 anaesthetised open-chest dogs. One group (n = 8) was studied before and afer 1 mg . kg-1 propranolol intravenously; a second group (n = 5) served as controls. Simultaneous blood samples were drawn from arterial and coronary sinus catheters for measurement of lactate and catecholamine concentrations. In controls, coronary artery constriction resulted in a reproducible fall in fractional myocardial lactate extraction and an increase in left atrial pressure, but caused no significant changes in blood pressure, heart rate or plasma concentrations of noradrenaline, adrenaline, or dopamine. In the treated group, heart rate was reduced but blood pressure was the same after propranolol; both remained unchanged during constriction and after release. The fall in fractional lactate extraction was abolished by propranolol. Arterial noradrenaline increased significantly after propranolol, fell during constriction and rose again after release. A similar trend was observed in coronary sinus noradrenaline. Reversible myocardial ischaemia is not associated with peripheral or myocardial release of catecholamines. Pre-treatment with propranolol appears to exert a protective effect on the myocardium even during reversible ischaemia. Although peripheral noradrenaline levels are increased after propranolol, this increase is not maintained during coronary artery constriction.

Acute Disease↗
PubMed1980

Role of cortisol ion cardiac glucose metabolism in vivo.

Little is known about how physiological concentrations of glucocorticoid relate to cardiac metabolism in vivo. Healthy conscious dogs with catheters implanted for blood sampling and glucose infusion were studied. The range of blood glucose values produced by glucose infusion was 3700 to 74,400 mumol/liter. Arterial glucose concentration (Ca) was not significantly correlated with the arterial-coronary sinus difference in concentration of glucose, Ca-cs glucose (N = 50, r = 0.23). However, at or above glucose infusion rates of 2120 mumol/min, significant increases in cardiac glucose extractions were seen. The range of plasma cortisol values was 13 to 438 nmol/liter. Cortisol immunoreactivity in arterial plasma (Ia cortisol) was significantly and negatively correlated with Ca-cs glucose (N = 50, r = -0.37, P < 0.01). Nonparametric analysis confirmed this association (Spearman rank correlation coefficient, rs = -0.44, P < 0.01). The heart took up and released cortisol in relation to Ia cortisol (N = 50, r = 0.75, P < 0.001; rs = 0.58, P < 0.001). The range of Ia-cs cortisol was -31 to 138 nmol/liter (mean +/- SEM, 12 +/- 4, P < 0.01). The Ca-cs glucose was negatively correlated with Ia-cs cortisol (N = 50, r = -0.43, P < 0.01; rs = 0.50, P < 0.001). Thus, higher plasma cortisol immunoreactivity may lead to greater myocardial cortisol extraction and suppression of myocardial glucose extraction in vivo. At the same time arterial insulin immunoreactivity had a significant positive relationship to myocardial glucose extraction (N = 50, r = 0.37, P < 0.05; rs = 0.38, P < 0.01) and arterial plasma free fatty acids a negative relationship (N = 50, rs = -0.30, P < 0.05).

Animals↗